Solid-State Hydration/Dehydration of Erythromycin A Investigated by ab Initio Powder X‑ray Diffraction Analysis: Stoichiometric and Nonstoichiometric Dehydrated Hydrate

The
stable dihydrate crystalline phase (DH) of erythromycin
A loses water upon heating to give the anhydrous phase I (AI). Further heating then results in a polymorphic transformation via
the amorphous state (melt) to give another anhydrous phase II (AII). The anhydrous phases of AI and AII undergo hydration when increasing the humidity. The crystals of AI showed stoichiometric hydration to give DH, whereas the crystals of AII showed nonstoichiometric
hydration to give the humidity dependent nonstoichiometric hydrate
phase (NSH). The crystal structures of AI and AII were directly determined from powder X-ray
diffraction data using the direct space strategy for the structure
solution followed by Rietveld refinement. From the structural properties
of AI and AII, aspects of the mechanism
of the solid-state transformations of DH and the hydration
behavior of AI and AII have been determined,
and the importance of the hydrophilicity of the voids has been revealed.